Evidence map›Paper›PMID 36660164›Full record

ArticleNature physics2023

Enhanced statistical sampling reveals microscopic complexity in the talin mechanosensor folding energy landscape.

Rafael Tapia-Rojo, Marc Mora, Stephanie Board, Jane Walker, Rajaa Boujemaa-Paterski, Ohad Medalia, Sergi Garcia-Manyes

Open access · bronzeAbstract read
In one paragraph

Article in Nature physics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.4field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Universal cold RNA phase transitions.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. A Hierarchical Mechanotransduction System: From Macro to Micro.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  14. Folding kinetics of an entangled protein.PLoS computational biology · 2023
    Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Rafael Tapia-Rojo *Single Molecule Mechanobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, London, UK.
Marc Mora *Single Molecule Mechanobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, London, UK.
Stephanie BoardSingle Molecule Mechanobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, London, UK.
Jane WalkerSingle Molecule Mechanobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, London, UK.
Rajaa Boujemaa-PaterskiDepartment of Biochemistry, Zurich University, Winterhurerstrasse 190, CH-8057, Zurich, Switzerland.
Ohad MedaliaDepartment of Biochemistry, Zurich University, Winterhurerstrasse 190, CH-8057, Zurich, Switzerland.
Sergi Garcia-ManyesSingle Molecule Mechanobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, London, UK.
King's College London · GBZHAW Zurich University of Applied Sciences · CH

Funding

Cancer Research UK FC001002Wellcome Trust 212218Wellcome Trust FC001002
6 · The paper itself

Abstract

Statistical mechanics can describe the major conformational ensembles determining the equilibrium free-energy landscape of a folding protein. The challenge is to capture the full repertoire of low-occurrence conformations separated by high kinetic barriers that define complex landscapes. Computationally, enhanced sampling methods accelerate the exploration of molecular rare events. However, accessing the entire protein's conformational space in equilibrium experiments requires technological developments to enable extended observation times. We developed single-molecule magnetic tweezers to capture over a million individual transitions as a single talin protein unfolds and refolds under force in equilibrium. When observed at classically-probed timescales, talin folds in an apparently uncomplicated two-state manner. As the sampling time extends from minutes to days, the underlying energy landscape exhibits gradually larger signatures of complexity, involving a finite number of well-defined rare conformations. A fluctuation analysis allows us to propose plausible structures of each low-probability conformational state. The physiological relevance of each distinct conformation can be connected to the binding of the cytoskeletal protein vinculin, suggesting an extra layer of complexity in talin-mediated mechanotransduction. More generally, our experiments directly test the fundamental notion that equilibrium dynamics depend on the observation timescale.

Identifiers

PMID36660164
PMCPMC7614079
OpenAlexW4308458589

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.